Genetic heterogeneity is observed for many Mendelian, single gene disorders. While environmental influences provide minor contributions, variations in phenotypic outcome are generally attributable to allelic heterogeneity or genetic modifier genes, allelic variants distinct from the mutant gene, which can affect disease onset, progression, and outcome by either increasing or reducing disease severity. As such, prior to the invention described herein, there was a pressing need to identify genetic modifiers of disease.